Sodium Zirconium Research Articles

Shortening synthesis process of zirconium hydroxide as a hydrolysis product of sodium zirconate

This research was focusing on shortening the process of Zirconium hydroxide (Zr(OH)<sub>4</sub>) synthesis to get a more efficient process. In the earlier method, Zr(OH)<sub>4</sub> was produced through ZOC, which was the product of Na<sub>2</sub>ZrO<sub>3</sub> reacted with HCl. While this study offers a new method to synthesize Zr(OH)<sub>4</sub> through the hydrolysis process of sodium zirconate (Na<sub>2</sub>ZrO<sub>3</sub>), removing the leaching step of Na<sub>2</sub>ZrO<sub>3</sub> with HCl. The hydrolysis process of Na<sub>2</sub>ZrO<sub>3</sub> was carried out in a multistage stirred reactor at 70 °C. The multistage hydrolysis process occurred in 13 stages with 4000 grams of feed and 890 liters of water. This process produced 2500 grams of Zr(OH)<sub>4</sub>. Then the impurities analysis was done using UV-Vis and atomic absorption spectroscopy (SAA). The UV-Vis analysis was done to analyze Si concentration, while the atomic absorption spectroscopy (SAA) was done to analyze Na concentration. Si and Na concentrations could decrease to 23.98 µg/ml and 1.05 µg/ml, respectively. The Zr(OH)<sub>4</sub> contained in the residue was characterized using X-Ray Diffractometer (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). Then, the calcination process of Zr(OH)<sub>4</sub> was done at 300 °C and 400 °C for 1 hour, and characterized using XRD. The XRD result shows crystals of zirconium titanium oxide or srilankite, and SiO<sub>2</sub> crystals that are separated from ZrO<sub>2</sub> or TiO<sub>2</sub> crystals. Surface analysis was done using Scanning Electron Microscope – Energy Dispersive X-Ray (SEM-EDX), the result shows that the hydrolysis process at the 3<sup>rd</sup>, 7<sup>th</sup>, and 13<sup>th</sup> stages have different amorphous crystals with bright colors. At the 13th hydrolysis stage, Zr concentration increased to 63.38%, and Si concentration decreased. Thus, the shorter process of Zr(OH)<sub>4</sub> synthesis has been done successfully.

EE3 Cost Estimation of Published Heart Failure and Edema Events in Hyperkalemic Patients on Patiromer and Sodium Zirconium Cyclosilicate

Risk of real-world hospitalizations for heart failure (HHF), and edema hospitalizations or emergency department (ED) visits (edema events) were previously directly compared by Zhuo et al (J Card Fail 2022;28:1414–23) for patients on patiromer (PAT) or sodium zirconium cyclosilicate (SZC), and showed consistent numerical differences across all endpoints favoring PAT. Statistical significance was achieved on the secondary endpoint of edema events and in a subgroup of patients who did not have HF prior to index HHF event. These numeric differences warrant further investigation as they may have economic and/or clinical importance.

HSD13 Emergency Department Hyperkalemia Outcomes Are Improved with Newer Potassium Binders

Hyperkalemia is an expensive and potentially fatal Emergency Department (ED) presentation. This study aimed to compare outcomes in ED patients with hyperkalemia who received potassium binders, including patiromer, sodium zirconium cyclosilicate (SZC), binder sodium polystyrene sulfonate (SPS), or no binder.

EE341 Cost Effectiveness of Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia in Mexico

To perform a cost-effectiveness evaluation from the perspective of the Mexican Health System (MHS), of the use of sodium zirconium cyclosilicate (SZC) for the treatment of hyperkalemia (HK) in patients with chronic kidney disease (CKD) and/or heart failure (HF).

Comparison of Sodium Zirconium Cyclosilicate to Sodium Polystyrene Sulfonate in the Inpatient Management of Acute Hyperkalemia

Background: Oral potassium binders have a role in the management of acute hyperkalemia among hospitalized patients. However, with therapeutic additions to this class, there is insufficient evidence between potassium binders to support a standard of care recommendation for use in this acute setting. Objective: The purpose of this study was to compare the acute potassium lowering effects of sodium zirconium cyclosilicate (SZC) and sodium polystyrene sulfonate (SPS). Methods: A retrospective review of admitted patients who received SZC or SPS was conducted after exemption from the Institutional Review Board. Patients with baseline potassium values less than 5.1 mmol/L or factors contributing to potentially false report of serum potassium were excluded. The primary outcome was the average change in potassium from baseline to 24 hours following potassium binder administration. Secondary outcomes compared changes to potassium from baseline to various time periods after administration, presence of electrolyte changes, and documentation of serious adverse events. Results: A total of 246 patients were included, with 128 receiving SZC and 118 receiving SPS. Mean change in serum potassium (mmol/L) at 24 hours was not significant between binders (−.78 vs −.91; P = .22). Secondary efficacy and safety outcomes were also similar between groups. A total of 5 serious adverse events were reported, occurring only in the SPS group. Conclusion: SZC and SPS have comparable effects in acute potassium reduction, with serious gastrointestinal adverse events documented only in SPS patients. Health systems may consider this data in determining medication formularies or during order set development.

P330 MANAGEMENT OF HYPERKALEMIA IN A PATIENT WITH HFREF

Abstract Hyperkalimia (HK) is a condition that occurs very frequently in patients with heart failure (HF). HK often limits and discourages the implementation and optimization of RAASI therapy in patients with HFrEF. The introduction of the new K–binders drugs has made it possible to overcome this obstacle by allowing optimization of therapy even in patients with persistent hyperkalemia. Mr. AB aged 83 years cognitively intact and autonomous ( Katz‘s BADL and Lawton‘s IADL preserved; MMSE 29/30). February 2022 accessed DEA for aggravating exertional dyspnea; at that time echocardiogram finding reduced left ventricular systolic function, FE 35%. March 2022 performed elective coronarography: coronary tree free of critical lesions, confirmed on echocardiogram reduced FE. Post indication to undertake Sacubitril/Valsartan, beta blocker and SGLT2i therapy. For moderate CKD (eGFR 33 ml/min) with tendency to hyperkalemia not initiated MRA. April 2022 the patient was taken to our Heart Failure Outpatient Clinic–UTIG– AOU Careggi. June 2022 considered improvement in renal function and Kaliemia in optimized range GDMTs therapy with Potassium Canreonate 25 mg/day. At control EEs in July 2022 found hyperKalemia with K values 5.5 mEq/L but stability of renal function. Reduced therefore the dosage of Potassium Canreonate (25 mg every other day) with indication to repeat blood tests soon. September 2022 despite reduction in MRA dosage further increase in Kaliemia values to 5.8 mEq/L. Suspended Potassium Canreonate and started Sodium Zirconium Cyclosilicate therapy initially at loading dosage of 10 g three times daily for two days then continued with maintenance dosage of 5 g. At follow–up performed the following week K 4.5 mEq/L. Re–introduced Potassium Canreonate 25 mg/day with initial tight control of potassium values that remained stably at optimal values. Hyperkalemia is an obstacle in titrating HFrEF, especially in elderly patients with CKD. However, we have new drugs available that may allow the implementation of guideline–recommended treatments by controlling potassium values.

Real-World Modifications of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Hyperkalemia Initiating Sodium Zirconium Cyclosilicate Therapy: The OPTIMIZE I Study.

Hyperkalemia (HK) may result in disruptions of guidelines-concordant renin-angiotensin-aldosterone system inhibitors (RAASi), a standard of care in persons with chronic kidney disease (CKD). Such disruptions-dose reduction or discontinuation-diminish the benefits of RAASi, placing patients at risk of serious events and renal dysfunction. This real-world study evaluated RAASi modifications among patients who initiated sodium zirconium cyclosilicate (SZC) for HK. Adults (≥ 18years) initiating outpatient SZC (index date) while on RAASi were identified from a large US claims database (January 2018-June 2020). RAASi optimization (maintain same or up-titration of RAASi dosage), non-optimization (down-titration of RAASi dosage or discontinuation), and persistence were descriptively summarized following index. Predictors of RAASi optimization were assessed using multivariable logistic regression models. Analyses were conducted by subgroups, including patients without end-stage kidney disease (ESKD), with CKD, and with CKD + diabetes. A total of 589 patients initiated SZC during RAASi therapy (mean age 61.0years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up = 8.1months). Most patients (77.4%) optimized RAASi therapy after initiating SZC; 69.6% maintained the same dosage while 7.8% had up-titrations. A similar rate of RAASi optimization was observed among subgroups without ESKD (78.4%), with CKD (78.9%), and with CKD + diabetes (78.1%). At 1-year post-index, 73.9% of all patients who optimized RAASi were still on therapy, while only 17.9% of patients who did not optimize therapy were still on a RAASi. Among all patients, predictors of RAASi optimization included fewer prior hospitalizations (odds ratio = 0.79, 95% CI [0.63-1.00]; p < 0.05) and fewer prior emergency department (ED) visits (0.78 [0.63-0.96]; p < 0.05). Consistent with clinical trial findings, nearly 80% of patients who initiated SZC for HK optimized their RAASi therapy. Patients may require long-term SZC therapy to encourage continuation of RAASi therapy especially after inpatient and ED visits.

Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.

Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.

Evaluation of the effect of sodium zirconium cyclosilicate on arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with hyperkalaemia: protocol for the multicentre, randomised, controlled DIALIZE-Outcomes study

IntroductionPatients with kidney failure receiving chronic haemodialysis have elevated risk of arrhythmias potentially increasing the likelihood of sudden cardiac death, stroke and hospitalisation. The DIALIZE study (NCT03303521) demonstrated that sodium...

In pursuit of balance: renin-angiotensin-aldosterone system inhibitors and hyperkalaemia treatment.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.

Sodium polystyrene is unsafe and should not be prescribed for the treatment of hyperkalaemia: primum non nocere!

'Old-generation' potassium (K) binders [i.e. sodium (SPS) and calcium polystyrene sulfonate] are widely used, but with substantial heterogeneity across countries to treat hyperkalaemia (HK). However, there are no randomized data to support their chronic use to manage HK, nor have they been shown to have a renin-angiotensin-aldosterone system inhibitor (RAASi)-enabling effect. These compounds have poor tolerability and an unpredictable onset of action and magnitude of K lowering. Furthermore, SPS may induce fluid overload, owing to the fact that it exchanges K for sodium. Its use has also been associated with colonic necrosis, as emphasized by a black box warning from the US Food and Drug Administration. In contrast, two new K binders, patiromer and sodium zirconium cyclosilicate, have been shown to be safe and well tolerated for chronic management of HK, thereby enabling RAASi optimization, as acknowledged by the latest international cardiorenal guidelines. In view of the lack of reliable evidence regarding the efficacy and safety of the old-generation K binders compared with the placebo-controlled randomized and real-word evidence demonstrating the safety, efficacy and RAASi-enabling effect of the new K binders, clinicians should now use these new K binders to treat HK (primum non nocere!).

Pharmacological strategies to manage hyperkalaemia: out with the old, in with the new? Not so fast….

Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events.

Fecal Ammonium in mice with CKD: gastrointestinal sequestration by SZC.

Background: Urinary Ammonium (NH4+) excretion is decreased in CKD but very little is known about fecal NH4+excretion. Sodium Zirconium Cyclosilicate (SZC) is a cation-exchanger that selectively captures K+ in the gastrointestinal tract. We investigated if SZC can sequester NH4+ in vivo and evaluated the effect of SZC on fecal NH4+ in a mouse model of CKD. Methods: Mice with CKD induced by 5/6 kidney ablation were fed either a regular diet or a diet containing SZC (4g/Kg) and followed for 7 days. Feces NH4+ was measured before and after addition of 50 mEq KCl/L to release NH4+ from SZC. NH4+ sequestered in SZC in the gastrointestinal tract was estimated from the delta fecal NH4+observed when KCl was added to liberate the sequestered NH4+. Results: In mice with CKD fecal NH4+ excretion was higher than in normal mice and also higher than urine NH4+ excretion measured concurrently. Using data pooled from the SZC diet, the delta NH4+ was 6.5 ± 0.6 as compared to 0.6 ± 0.6 µmol/g on the normal diet p<0.0001. Conclusions:Fecal NH4+ excretion in CKD is increased and about 6-fold higher than urine NH4+ excretion revealing an important route of elimination of NH4+ present in the GI tract. SZC administration sequesters a substantial portion of NH4+ in the GI tract suggesting that the binding of NH4+ offers therapeutic potential beyond its known primary action as a specific K+ binder.

A randomized study to compare oral potassium binders in the treatment of acute hyperkalemia

BackgroundThe KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy.MethodsEmergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics).DiscussionThe findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia.Trial registrationClinicalTrials.gov Identifier: NCT04585542. Registered 14 October 2020.

Delivery of sodium zirconium cyclosilicate through gastric and enteral feeding tubes.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease.

Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)-an oral, highly selective potassium (K+) binder-compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b-5 CKD and/or estimated glomerular filtration rate <45mL/min/1.73 m2, within 3months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0-≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2-21days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5-5.0mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180days. The primary endpoint is the occurrence of normokalemia at 180days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin-angiotensin-aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated.Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021.

Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease.

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

Use of tecovirimat for mpox infection followed by JYNNEOS vaccination postinfection in a liver transplant recipient.

Use of tecovirimat for mpox infection followed by JYNNEOS vaccination postinfection in a liver transplant recipient.

Evaluation of safety, effectiveness and treatment patterns of sodium zirconium cyclosilicate in management of hyperkalaemia in China: a real-world study protocol

IntroductionHyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium...

Single Dose of Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate in Hospitalized Patients With Hyperkalemia.

Sodium zirconium cyclosilicate (SZC) is an inorganic zirconium silicate compound that selectively exchanges potassium for hydrogen and sodium. "Once" doses of SZC (with option to redose) in patients with hyperkalemia in hospitalized settings have not been evaluated. We hypothesized that a once dose of SZC would be non-inferior to sodium polystyrene sulfonate (SPS) in reducing serum potassium. The objective of our study is to evaluate the effect of a "once" dose of SZC when compared with SPS in reducing serum potassium levels. This was a retrospective analysis of patients who received either a "once" dose of SZC or single or repeated doses of SPS for hyperkalemia. The primary endpoint was mean absolute reduction in the first serum potassium value at least 4 hours after administration. The secondary efficacy endpoints were the rate of additional potassium-lowering therapies and the rate of normokalemia within 48 hours. Safety endpoints were the incidence of electrolyte abnormalities, hypoglycemia, hypertension, hypotension, and colonic necrosis. A total of 260 patients were included in the analysis. The mean initial serum potassium was similar between groups (5.6 ± 0.4). The absolute serum potassium reduction was -0.88 ± 0.64 mEq/L and -0.75 ± 0.65 mEq/L with SZC and SPS, respectively. The "once" regimen of SZC demonstrated non-inferiority compared with SPS (P < 0.0001). The proportion of patients achieving normokalemia within 48 hours and the proportion of patients receiving additional potassium-lowering therapies did not differ between groups. The "once" dose regimen (with redose option) of SZC was non-inferior to the "once" or repeated dosing regimen of SPS with regard to absolute potassium reduction. There were no significant differences in the rate of additional potassium-lowering therapies and the rate of normokalemia at 48 hours. The incidence of hypertension was less common among patients who received SZC.